Phase 1
Completed N=16
GSK1325756 Relative Bioavailability Study in Healthy Elderly Subjects
Pulmonary Disease, Chronic Obstructive
Source: ClinicalTrials.gov NCT03457727 ↗
Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Aug 2019
Primary outcomePrimary: Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1 — 6166.7; 6052.9; 5816.4; 5996.1 Hours*nanograms per milliliter
Summary
This 2-part study will be carried out on healthy elderly subjects to evaluate relative bioavailability of danirixin formulations. Part A will support the selection of the formulation and Part B will assess food effect, bioavailability and pharmacokinetic (PK) profile of selected formulation from Part A. Danirixin is currently administered with food, therefore the investigation of food effect for the selected formulation could potentially enable dosing without food. Approximately 16 subjects will be included in Part A and approximately 24 subjects will be included in Part B. Both parts will include a screening phase, treatment phase with in-between washout period and a follow-up phase.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 1 |
6166.7; 6052.9; 5816.4; 5996.1; 11394.6; 11285.7 | — |
| PRIMARY Maximum Observed Concentration (Cmax) of Danirixin for Part 1 |
761.5; 712.8; 762.3; 659.2; 2708.2; 2418.5 | — |
| PRIMARY Number of Participants With Any Adverse Event (AE) and Serious Adverse Events (SAEs) in Part 1 |
1; 0; 0; 0; 2; 1 | — |
| PRIMARY Number of Participants With Vital Signs of Potential Clinical Concern in Part 1 |
2; 2; 2; 2; 0; 0 | — |
| PRIMARY Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 1 |
1; 2; 2; 2; 2; 1 | — |
| PRIMARY Number of Participants With Laboratory Values of Potential Clinical Concern in Part 1 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 1 |
5515.9; 5573.6; 5524.7; 5287.0; 11480.1; 10977.2 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to 24 Hours Post-dose (AUC [0-24]) of Danirixin for Part 1 |
4919.5; 4952.0; 4984.8; 4705.2; 10744.8; 10419.9 | — |
| SECONDARY Time to Occurrence of Cmax (Tmax) of Danirixin for Part 1 |
3.897; 3.653; 3.585; 4.158; 1.165; 1.331 | — |
| SECONDARY Terminal Half-life (t1/2) of Danirixin for Part 1 |
9.638; 10.904; 8.916; 9.888; 8.298; 9.498 | — |
| SECONDARY Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 1 |
47.660; 47.587; 44.657; 44.757; 44.372; 41.789 | — |
| SECONDARY Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) of Danirixin for Part 1 |
0.323; 0.383; 0.383; 0.511; 0.000; 0.065 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to Infinity (AUC [0-inf]) of Danirixin for Part 2 |
12426.4; 7761.2; 8136.7; 7356.4; 14615.2; 10185.0 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to t (AUC [0-t]) of Danirixin for Part 2 |
12026.9; 7484.2; 7757.2; 6986.9; 12903.9; 9023.8 | — |
| SECONDARY Area Under the Concentration-time Curve From Time 0 to 24 Hours (AUC [0-24]) of Danirixin for Part 2 |
11096.7; 6482.2; 6706.6; 6187.1; 12762.9; 8681.0 | — |
| SECONDARY Maximum Observed Concentration (Cmax) of Danirixin for Part 2 |
2317.4; 989.9; 969.9; 1019.8; 2292.5; 1389.7 | — |
| SECONDARY Time to Maximum Observed Concentration (Tmax) of Danirixin for Part 2 |
1.271; 3.749; 4.150; 3.355; 1.978; 2.887 | — |
| SECONDARY Terminal Half-life (t1/2) of Danirixin for Part 2 |
10.647; 11.424; 11.484; 11.652; 11.304; 10.913 | — |
| SECONDARY Time to Last Quantifiable Concentration (Tlast) of the Blood Concentration of Danirixin for Part 2 |
45.139; 47.144; 47.200; 46.741; 45.217; 45.242 | — |
| SECONDARY Lag Time Before Observable Concentration (Tlag) of Danirixin for Part 2 |
0.000; 0.283; 0.641; 0.386; 0.000; 0.423 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) and Serious Adverse Events in Part 2 |
1; 1; 1; 0; 0; 0 | — |
| SECONDARY Number of Participants With Vital Signs of Potential Clinical Concern in Part 2 |
2; 3; 4; 4; 4; 3 | — |
| SECONDARY Number of Participants With 12-lead Electrocardiogram (ECG) Values of Potential Clinical Concern in Part 2 |
1; 2; 1; 3; 1; 2 | — |
| SECONDARY Number of Participants With Laboratory Values of Potential Clinical Concern in Part 2 |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
- Subjects must be 65 to 80 years of age inclusive, at the Screening Visit.
- Subjects who are healthy, as determined by a responsible and experienced physician, based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring or a subject with a clinical abnormality or laboratory parameters outside the reference range for the population being studied may be included if the investigator and the GlaxoSmithKline (GSK) Medical Monitor agree that the finding is unlikely to introduce risk factors and will not interfere with the study procedures and objectives. Additionally, laboratory assessments that are specifically listed in the inclusion or exclusion criteria and are outside of the reference range can be repeated once during the screening period.
- Body weight >=50 kilograms (kg) and body mass index (BMI) within the range 19 - 34 kg per meter square (kg/m^2) (inclusive).
- Male or female subjects will be included. A female subject is eligible to participate if she is not pregnant, not breastfeeding, and at least one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or a WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 60 hours after the last dose of study treatment.
- Capable of giving signed informed consent.
- AST, ALT, alkaline phosphatase and bilirubin 1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin 1.5x ULN
- Bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 milliseconds (msec).
- Use of prescription or non-prescription drugs, including proton pump inhibitors, histamine receptor 2 antagonists, systemic antacid medications (unless these can be held during the study), vitamins, herbal and dietary supplements (including St John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) prior to the first dose of study treatment until completion of the last study assessment , unless in the opinion of the investigator and GSK Medical Monitor, the medication will not interfere with the study procedures or compromise subject safety. Some examples of exceptions (permitted medications) are: Stable dose of anti-hypertensive medication for at least 3 months prior to the screening visit; Stable dose of lipid-lowering medications (statins or fibrates) for at least 3 months prior to the screening visit; Antacids up to 24 hours prior to dosing.
- Participation in the study would result in loss of blood or blood products in excess of 500 milliliter (mL) within 3 months.
- The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 3 months, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
- Exposure to more than 4 new chemical entities within 12 months prior to the first dosing day.
- Participation in a previous clinical trial with danirixin within 1 year prior to the first dosing day in the current study.
- Female Subjects: Positive urine beta-human chorionic gonadotropin (beta-hCG) test at screening.
- Presence of Hepatitis B surface antigen (HBsAg) at screening Positive Hepatitis C antibody test result at screening.
- Positive Hepatitis C ribonucleic acid (RNA) test result at screening or within 3 months prior to first dose of study treatment.
- For potent immunosuppressive agents, presence of the Hepatitis B core antibody (HBcAb) should also lead to exclusion from the study even if HBsAg is negative.
- Positive pre-study drug/alcohol screen.
- Positive human immunodeficiency virus (HIV) antibody test.
- Regular use of known drugs of abuse.
- Regular alcohol consumption within 6 months prior to the study defined as: an average weekly intake of >21 units fo
Data sourced from ClinicalTrials.gov (NCT03457727). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.